title: Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.
abstract: Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.
authors.affiliation: Centre de recherche de l'Institut Universitaire de Cardiologie et Pneumologie de Québec, Hôpital Laval, Québec, Canada;
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Laplante
authors.forename: Alexandre
authors.initials: A
authors.lastname: Charbonneau
authors.forename: Rita Kohen
authors.initials: RK
authors.lastname: Avramoglu
authors.forename: Patricia
authors.initials: P
authors.lastname: Pelletier
authors.forename: Xiangping
authors.initials: X
authors.lastname: Fang
authors.forename: Hélène
authors.initials: H
authors.lastname: Bachelard
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
authors.forename: Patrick
authors.initials: P
authors.lastname: Mathieu
authors.forename: André
authors.initials: A
authors.lastname: Marette
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006651:Histocytochemistry; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D014280:Triglycerides / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary; D014280:Triglycerides
keywords: atherosclerosis; diabetes; endothelial function; obesity